The State Scientific Automated Medical Registry, Kazakhstan: an important resource for low-dose radiation health research.

Direct quantitative assessment of health risks following exposure to ionizing radiation is based on findings from epidemiological studies. Populations affected by nuclear bomb testing are among those that allow such assessment. The population living around the former Soviet Union's Semipalatinsk nuclear test site is one of the largest human cohorts exposed to radiation from nuclear weapons tests. Following research that started in the 1960s, a registry that contains information on more than 300,000 individuals residing in the areas neighboring to the test site was established. Four nuclear weapons tests, conducted from 1949 to 1956, resulted in non-negligible radiation exposures to the public, corresponding up to approximately 300 mGy external dose. The registry contains relevant information about those who lived at the time of the testing as well as about their offspring, including biological material. An international group of scientists worked together within the research project SEMI-NUC funded by the European Union, and concluded that the registry provides a novel, mostly unexplored, and valuable resource for the assessment of the population risks associated with environmental radiation exposure. Suggestions for future studies and pathways on how to use the best dose assessment strategies have also been described in the project. Moreover, the registry could be used for research on other relevant public health topics.

The Krümmel (Germany) Childhood Leukaemia Cluster: a review and update.

The debate surrounding possible adverse health effects from the civil use of nuclear power under normal operating conditions has been on-going since its introduction. It was particularly intensified by the detection of three leukaemia clusters near nuclear installations, i.e. near the reprocessing plants in Sellafield and Dounreay, UK, and near the Krümmel nuclear power plant, Germany, the last of which commenced between 1990 and 1991 and was first described in 1992; it continued until 2003, and an elevated risk up to 2005 has been reported in the literature. A number of expert commissions and working groups were set up by the governments of the German federal states of Lower Saxony and Schleswig-Holstein to investigate the possible causes of the cluster. An overview of the many risk factors that were investigated as a possible explanation of the Krümmel cluster is given here, focussing on radiation, but also including other risk factors. Further, results from related epidemiological and cytogenetic studies are described. In summary, the cause of the occurrence of the Krümmel cluster has to be considered as unknown. Further research on the causes of childhood leukaemia is needed, focussing on epigenetics and on gene-environment interaction. An update of the leukaemia incidence around the Krümmel site shows that the incidence rates are now comparable to the average rate in Germany.

[Effects on health of the Chernobyl accident: 30 years on]. / Gesundheitliche Folgen des Unfalls von Tschernobyl - 30 Jahre danach.

This paper reflects the current state of research into the short- and long-term effects on health in the former Soviet Union and Europe of the nuclear accident in Chernobyl. It discusses the latest results of epidemiological studies and presents future research perspectives.

The German Thorotrast Cohort Study: a review and how to get access to the data.

It is well known that exposures like those from (226)Ra, (224)Ra and Thorotrast(®) injections increase the risk of neoplasia in bone marrow and liver. The thorium-based radioactive contrast agent Thorotrast(®) was introduced in 1929 and applied worldwide until the 1950s, especially in angiography and arteriography. Due to the extremely long half-life of several hundred years and the life-long retention of the thorium dioxide particles in the human body, patients suffer lifetime internal exposure. The health effects from the incorporated thorium were investigated in a few cohort studies with a German study being the largest among them. This retrospective cohort study was set up in 1968 with a follow-up until 2004. The study comprises 2326 Thorotrast patients and 1890 patients of a matched control group. For those being alive at the start of the study in 1968 follow-up was done by clinical examinations on a biannual basis. For the others, causes of death were collected in various ways. Additionally, clinical, radiological and biophysical studies of patients were conducted and large efforts were made to best estimate the radiation doses associated with incorporation of the Thorotrast. The aim of this paper is to describe the cohort, important results and some open questions. The data from the German Thorotrast Study are available to other interested researchers. Information can be found at http://storedb.org .

Methods for Ensuring High Quality of Coding of Cause of Death. The Mortality Register to Follow Southern Urals Populations Exposed to Radiation.

BACKGROUND: To follow up populations exposed to several radiation accidents in the Southern Urals, a cause-of-death registry was established at the Urals Center capturing deaths in the Chelyabinsk, Kurgan and Sverdlovsk region since 1950. OBJECTIVES: When registering deaths over such a long time period, quality measures need to be in place to maintain quality and reduce the impact of individual coders as well as quality changes in death certificates. METHODS: To ensure the uniformity of coding, a method for semi-automatic coding was developed, which is described here. Briefly, the method is based on a dynamic thesaurus, database-supported coding and parallel coding by two different individuals. RESULTS: A comparison of the proposed method for organizing the coding process with the common procedure of coding showed good agreement, with, at the end of the coding process, 70 - 90% agreement for the three-digit ICD -9 rubrics. CONCLUSIONS: The semi-automatic method ensures a sufficiently high quality of coding by at the same time providing an opportunity to reduce the labor intensity inherent in the creation of large-volume cause-of-death registries.

A review of the results from the German Wismut uranium miners cohort.

The Wismut cohort is currently the largest single study on the health risks associated with occupational exposures to ionising radiation and dust accrued during activities related to uranium mining. The cohort has ∼59 000 male workers, first employed between 1946 and 1989, at the Wismut Company in Germany. The main effect is a statistically significant increase in mortality from lung cancer with both increasing cumulative radon exposure and silica dust exposure. Risks for cancers of the extrathoracic airways, all extra-pulmonary cancers and cardiovascular diseases associated with radiation exposures have been evaluated. Cohort mortality rates for some other cancer sites, stomach and liver, are statistically significantly increased in relation to the general population, but not statistically significantly related to occupational exposures. No associations between leukaemia mortality and occupational doses of ionising radiation were found.

Joint research towards a better radiation protection-highlights of the Fifth MELODI Workshop.

MELODI is the European platform dedicated to low-dose radiation risk research. From 7 October through 10 October 2013 the Fifth MELODI Workshop took place in Brussels, Belgium. The workshop offered the opportunity to 221 unique participants originating from 22 countries worldwide to update their knowledge and discuss radiation research issues through 118 oral and 44 poster presentations. In addition, the MELODI 2013 workshop was reaching out to the broader radiation protection community, rather than only the low-dose community, with contributions from the fields of radioecology, emergency and recovery preparedness, and dosimetry. In this review, we summarise the major scientific conclusions of the workshop, which are important to keep the MELODI strategic research agenda up-to-date and which will serve to establish a joint radiation protection research roadmap for the future.

Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research.

Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.

National radon programmes and policies: the RADPAR recommendations.

Results from epidemiological studies on lung cancer and radon exposure in dwellings and mines led to a significant revision of recommendations and regulations of international organisations, such as WHO, IAEA, Nordic Countries, European Commission. Within the European project RADPAR, scientists from 18 institutions of 14 European countries worked together for 3 y (2009-12). Among other reports, a comprehensive booklet of recommendations was produced with the aim that they should be useful both for countries with a well-developed radon programme and for countries with little experience on radon issues. In this paper, the main RADPAR recommendations on radon programmes and policies are described and discussed. These recommendations should be very useful in preparing a national action plan, required by the recent Council Directive 2013/59/Euratom.

[The Fukushima nuclear accident: consequences for Japan and for us]. / Der Reaktorunfall von Fukushima: Folgen für Japan und uns.

The Fukushima accident was the consequence of a preceding 2-fold natural catastrophe: the earth quake of 11 March 2011 and the subsequent tsunami. Due to favourable winds and to evacuation measures the radiation exposure to the general population in Japan as a whole and with some exceptions in the region outside the evacuation zone, too, was low. In this article the attempt is made to give an estimate of health consequences to the public. This is based upon WHO's dose estimates, knowledge of the consequences of the Chernobyl accident, of the atmospheric nuclear bomb testing in Kazakhstan and on the risk of childhood leukaemia after low dose radiation exposure. For Germany, there was no radiation threat due to the accident. Nonetheless, the events in Japan made clear that the rules and standards that were developed for the case of a reactor accident need to be revised.

X-ray fluorescence microscopy for investigation of archival tissues.

Several recent efforts in the radiation biology community worldwide have amassed records and archival tissues from animals exposed to different radionuclides and external beam irradiation. In most cases, these samples come from lifelong studies on large animal populations conducted in national laboratories and equivalent institutions throughout Europe, North America, and Japan. While many of these tissues were used for histopathological analyses, much more information may still be obtained from these samples. A new technique suitable for imaging of these tissues is x-ray fluorescence microscopy (XFM). Following development of third generation synchrotrons, XFM has emerged as an ideal technique for the study of metal content, speciation, and localization in cells, tissues, and organs. Here the authors review some of the recent XFM literature pertinent to tissue sample studies and present examples of XFM data obtained from tissue sections of beagle dog samples, which show that the quality of archival tissues allows XFM investigation.

Lung cancer mortality in the European uranium miners cohorts analyzed with a biologically based model taking into account radon measurement error.

The biologically based two-stage clonal expansion (TSCE) model is used to analyze lung cancer mortality of European miners from the Czech Republic, France, and Germany. All three cohorts indicate a highly significant action of exposure to radon and its progeny on promotion. The action on initiation is not significant in the French cohort. An action on transformation was tested but not found significant. In a pooled analysis, the results based on the French and German datasets do not differ significantly in any of the used parameters. For the Czech dataset, only lag time and two parameters that determine the clonal expansion without exposure and with low exposure rates (promotion) are consistent with the other studies. For low exposure rates, the resulting relative risks are quite similar. Exposure estimates for each calendar year are used. A model for random errors in each of these yearly exposures is presented. Depending on the used technique of exposure estimate, Berkson and classical errors are used. The consequences for the model parameters are calculated and found to be mostly of minor importance, except that the large difference in the exposure-induced initiation between the studies is decreased substantially.

The European Radiobiological Archives: online access to data from radiobiological experiments is available now.

The European Radiobiological Archive can be accessed at no cost at https://era.bfs.de. The necessary ID and password can be obtained from the curators at era@bfs.de.

Occupational dust and radiation exposure and mortality from stomach cancer among German uranium miners, 1946-2003.

OBJECTIVES: 'Dusty occupations' and exposure to low-dose radiation have been suggested as potential risk factors for stomach cancer. Data from the German uranium miner cohort study are used to further evaluate this topic. METHODS: The cohort includes 58 677 miners with complete information on occupational exposure to dust, arsenic and radiation dose based on a detailed job-exposure matrix. A total of 592 stomach cancer deaths occurred in the follow-up period from 1946 to 2003. A Poisson regression model stratified by age and calendar year was used to calculate the excess relative risk (ERR) per unit of cumulative exposure to fine dust or from cumulative absorbed dose to stomach from α or low-LET (low linear energy transfer) radiation. For arsenic exposure, a binary quadratic model was applied. RESULTS: After adjustment for each of the three other variables, a statistically non-significant linear relationship was observed for absorbed dose from low-LET radiation (ERR/Gy=0.30, 95% CI -1.26 to 1.87), α radiation (ERR/Gy=22.5, 95% CI -26.5 to 71.5) and fine dust (ERR/dust-year=0.0012, 95% CI -0.0020 to 0.0043). The relationship between stomach cancer and arsenic exposure was non-linear with a 2.1-fold higher RR (95% CI 0.9 to 3.3) in the exposure category above 500 compared with 0 dust-years. CONCLUSION: Positive statistically non-significant relationships between stomach cancer and arsenic dust, fine dust and absorbed dose from α and low-LET radiation were found. Overall, low statistical power due to low doses from radiation and dust are of concern.

The European radiobiological archives: online access to data from radiobiological experiments.

For financial and ethical reasons, the large-scale radiobiological animal studies conducted over the past 50 years are, to a large extent, unrepeatable experiments. It is therefore important to retain the primary data from these experiments to allow reanalysis, reinterpretation and re-evaluation of results from, for example, carcinogenicity studies, in the light of new knowledge in radiation biology. Consequently, there is an imperative need to keep these data available for the research community. The European Radiobiological Archives (ERA) were developed to fulfill this task. ERA has become a unique archive, including information from almost all European long-term studies carried out between the 1960s and the 1990s. The legacy database was originally developed in a manner that precluded online use. Therefore, strong efforts were made to transform it into a version that is available online through the web. This went together with quality assurance measures, including first the estimation of the rate of non-systematic errors in data entry, which at 2% proved to be very low. Second, every data set was compared against two external sources of information. Standardization of terminology and histopathology is a prerequisite for meaningful comparison of data across studies and analysis of potential carcinogenic effects. Standardization is particularly critical for the construction of a database that includes data from different studies evaluated by pathologists in different laboratories. A harmonized pathology nomenclature with modern standard pathology terms was introduced. As far as possible, references for the various studies were directly linked to the studies themselves. Further, a direct link to the JANUS database was established. ERA is now in a position where it has the potential to become a worldwide radiobiological research tool. ERA can be accessed at no cost at https://era.bfs.de. An ID and password can be obtained from the curators at era@bfs.de .

Radon and risk of death from cancer and cardiovascular diseases in the German uranium miners cohort study: follow-up 1946-2003.

Data from the German uranium miners cohort study were analyzed to investigate the radon-related risk of mortality from cancer and cardiovascular diseases. The Wismut cohort includes 58,987 men who were employed for at least 6 months from 1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. By the end of 2003, a total of 3,016 lung cancer deaths, 3,355 deaths from extrapulmonary cancers, 5,141 deaths from heart diseases and 1,742 deaths from cerebrovascular diseases were observed. Although a number of studies have already been published on various endpoints in the Wismut cohort, the aim of the present analyses is to provide a direct comparison of the magnitude of radon-related risk for different cancer sites and cardiovascular diseases using the same data set, the same follow-up period and the same statistical methods. A specific focus on a group of cancers of the extrathoracic airways is also made here, due to the assumed high organ doses from absorbed radon progeny. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to radon in working level months (WLM) and its 95% confidence limits (CI). There was a statistically significant increase in the risk of lung cancer with increasing radon exposure (ERR/WLM = 0.19%; 95% CI: 0.17%; 0.22%). A smaller, but also statistically significant excess was found for cancers of the extrathoracic airways and trachea (ERR/WLM = 0.062%; 95% CI: 0.002%; 0.121%). Most of the remaining nonrespiratory cancer sites showed a positive relationship with increasing radon exposure, which, however, did not reach statistical significance. No increase in risk was noted for coronary heart diseases (ERR/WLM = 0.0003%) and cerebrovascular diseases (ERR/WLM = 0.001%). The present data provide clear evidence of an increased radon-related risk of death from lung cancer, some evidence for an increased radon-related risk of death from cancers of the extrathoracic airways and some other extrapulmonary cancers, and no evidence for mortality from cardiovascular diseases. These findings are consistent with the results of other miner studies and dosimetric calculations for radon-related organ doses.

Progress in updating the European Radiobiology Archives.

PURPOSE: The European Radiobiology Archives (ERA), together with corresponding Japanese and American databases, hold data from nearly all experimental animal radiation biology studies carried out between 1960 and 1998, involving more than 300,000 animals. The Federal Office for Radiation Protection, together with the University of Cambridge have undertaken to transfer the existing ERA archive to a web-based database to maximize its usefulness to the scientific community and bring data coding and structure of this legacy database into congruence with currently accepted semantic standards for anatomy and pathology. METHODS: The accuracy of the primary data input was assessed and improved. The original rodent pathology nomenclature was recoded to replace the local 'DIS-ROD' (Disease Rodent) formalism with Mouse Pathology (MPATH) and Mouse Anatomy (MA) ontology terms. A pathology panel sampled histopathological slide material and compared the original diagnoses with currently accepted diagnostic criteria. RESULTS: The overall non-systematic error rate varied among the studies between 0.26% and 4.41%, the mean error being 1.71%. The errors found have been corrected and the studies thus controlled have been annotated. The majority of the original pathology terms have been successfully translated into a combination of MPATH and MA ontology terms. CONCLUSIONS: ERA has the potential of becoming a world-wide radiobiological research tool for numerous applications, such as the re-analysis of existing data with new approaches in the light of new hypotheses and techniques, and using the database as an information resource for planning future animal studies. When the database is opened for new data it may be possible to offer long-term storage of data from recent and future animal studies.

Radon and risk of extrapulmonary cancers: results of the German uranium miners' cohort study, 1960-2003.

Data from the German miners' cohort study were analysed to investigate whether radon in ambient air causes cancers other than lung cancer. The cohort includes 58,987 men who were employed for at least 6 months from 1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. A total of 20,684 deaths were observed in the follow-up period from 1960 to 2003. The death rates for 24 individual cancer sites were compared with the age and calendar year-specific national death rates. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to radon in working level months (WLM). The number of deaths observed (O) for extrapulmonary cancers combined was close to that expected (E) from national rates (n=3340, O/E=1.02; 95% confidence interval (CI): 0.98-1.05). Statistically significant increases in mortality were recorded for cancers of the stomach (O/E=1.15; 95% CI: 1.06-1.25) and liver (O/E=1.26; 95% CI: 1.07-1.48), whereas significant decreases were found for cancers of the tongue, mouth, salivary gland and pharynx combined (O/E=0.80; 95% CI: 0.65-0.97) and those of the bladder (O/E=0.82; 95% CI: 0.70-0.95). A statistically significant relationship with cumulative radon exposure was observed for all extrapulmonary cancers (ERR/WLM=0.014%; 95% CI: 0.006-0.023%). Most sites showed positive exposure-response relationships, but these were insignificant or became insignificant after adjustment for potential confounders such as arsenic or dust exposure. The present data provide some evidence of increased risk of extrapulmonary cancers associated with radon, but chance and confounding cannot be ruled out.

Esophagus cancer and radiation exposure due to nuclear test fallout: an analysis based on the data of the Semipalatinsk historical cohort, 1960-1999.

This paper describes the Semipalatinsk historical cohort study and, in particular, examines the association between combined external and internal radiation exposure and esophagus cancer. Esophagus cancer is the most frequent single cancer site in the cause of death follow-up for the Semipalatinsk cohort. Set up in the 1960s, this historical cohort included 10 exposed settlements in the vicinity of the Semipalatinsk nuclear test site in East Kazakhstan as well as 6 comparison settlements in a low exposure area of the same region. The external and internal radiation doses to the population of the settlements under study were mainly due to local fallout from atmospheric nuclear testing (1949-1962). The database includes dosimetry and health information for 19.545 inhabitants of exposed and comparison villages in the Semipalatinsk region, comprising a total of 582.750 person-years of follow-up between 1960 and 1999. Cumulative effective dose estimates in this cohort range from 20 mSv to -4 Sv, with a mean dose of 634 mSv in the exposed group. Relative risks were calculated in terms of rate ratios, using a Poisson regression model for grouped person-time data. Esophagus cancer was found substantially elevated, with a statistically significant increase of the relative risk with dose and an ERR/Sv of 2.37 (1.45; 3.28) for the total cohort. If the data set was restricted to the exposed group only, the ERR/Sv was found considerably lower (0.18 (-0.16; 0.52)), whereas the dose-response remained significant only in women. Overall, our results based on the Semipalatinsk historical cohort indicate an association between fallout exposure and the risk of esophagus cancer that should be further investigated.